Coactivation of Janus Tyrosine Kinase (Jak)1 Positively Modulates Prolactin-Jak2 Signaling in Breast Cancer: Recruitment of ERK and Signal Transducer and Activator of Transcription (Stat)3 and Enhancement of Akt and Stat5a/b Pathways

Prolactin (PRL) receptors (PRLRs) have been con-sidered selective activators of Janus tyrosine ki-nase (Jak)2 but not Jak1, Jak3, or Tyk2. We now report marked PRL-induced tyrosine phosphoryla-tion of Jak1, in addition to Jak2, in a series of human breast cancer cell lines, including T47D, MCF7, and SKBR3. In contrast, PRL did not acti-vate Jak1 in immortalized, noncancerous breast epithelial lines HC11, MCF10A, ME16C, and HBL-100, or in CWR22Rv1 prostate cancer cells or MDA-MB-231 breast cancer cells. However, intro-duction of exogenous PRLR into MCF10A, ME16C, or MDA-MB-231 cells reconstituted both PRL-Jak1 and PRL-Jak2 signals. In vitro kinase assays veri-fied that PRL stimulated enzymatic activity of Jak